title: Lumican - derived peptides inhibit melanoma cell growth and migration.
abstract: Lumican, a small leucine-rich proteoglycan of the extracellular matrix, presents potent anti-tumor properties. Previous works from our group showed that lumican inhibited melanoma cell migration and tumor growth in vitro and in vivo. Melanoma cells adhered to lumican, resulting in a remodeling of their actin cytoskeleton and preventing their migration. In addition, we identified a sequence of 17 amino acids within the lumican core protein, named lumcorin, which was able to inhibit cell chemotaxis and reproduce anti-migratory effect of lumican in vitro. The aim of the present study was to characterize the anti-tumor mechanism of action of lumcorin. Lumcorin significantly decreased the growth in monolayer and in soft agar of two melanoma cell lines - mice B16F1 and human SK-MEL-28 cells - in comparison to controls. Addition of lumcorin to serum free medium significantly inhibited spontaneous motility of these two melanoma cell lines. To characterize the mechanisms involved in the inhibition of cell migration by lumcorin, the status of the phosphorylation/dephosphorylation of proteins was examined. Inhibition of focal adhesion kinase phosphorylation was observed in presence of lumcorin. Since cancer cells have been shown to migrate and to invade by mechanisms that involve matrix metalloproteinases (MMPs), the expression and activity of MMPs were analyzed. Lumcorin induced an accumulation of an intermediate form of MMP-14 (~59kDa), and inhibited MMP-14 activity. Additionally, we identified a short, 10 amino acids peptide within lumcorin sequence, which was able to reproduce its anti-tumor effect on melanoma cells. This peptide may have potential pharmacological applications.
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS FRE 3481, Université de Reims-Champagne-Ardenne, Reims, France.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pietraszek
authors.forename: Stéphane
authors.initials: S
authors.lastname: Brézillon
authors.forename: Corinne
authors.initials: C
authors.lastname: Perreau
authors.forename: Maria
authors.initials: M
authors.lastname: Malicka-Błaszkiewicz
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Maquart
authors.forename: Yanusz
authors.initials: Y
authors.lastname: Wegrowski
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007632:Keratan Sulfate / Q000737:chemistry / Q000378:metabolism*; D000071234:Lumican; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008546:Melanoma, Experimental; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D010446:Peptide Fragments; D010455:Peptides; C544543:lumcorin; D007632:Keratan Sulfate; D051416:Focal Adhesion Protein-Tyrosine Kinases; D053511:Matrix Metalloproteinase 14